The primary aim of this project is to understand how, the formation of myelin is impaired in animal models of the disease phenylketonuria (PKU) and relate the abnormalities in myelin with the abnormalities in EEG. In earlier studies administration of either phenylalanine (phe) alone or p-chlorophenylalanine (pcpa) plus phe to immature rats was used to simulate PKU in animals. Recently we evaluated the method of alpha methylphenylalanine (alpha mpa) plus phe treatment for inducing PKU in rats. Like in genetic PKU, all the three methods of inducing PKU resulted in myelin deficiency. It has been shown that treatment with steroid hormones enhance myelination. We therefore plan to determine if treatment with steroid hormones of PKU animals will overcome the myelin deficiency. Reduction in the proportion of unsaturated fatty acids observed in the myelin from PKU rats may alter the physicochemical properties of the membrane. Since metabolism of inositol phosphatides and the physicochemical properties of the membrane are interrelated we will determine if the metabolism of inositol phosphatides in brain is altered in PKU animals. The value of brainstem auditory evoked potentials (BAEP) latencies in assessing functional state of the central nervous system has been well documented. To relate abnormalities in EEG with myelin deficiency, in our earlier studies we examined the BAEP latencies in experimental PKU in immature rats and in triethyltin-induced edema (demyelination in young adult rats). We recently compared the BAEP latencies in myelin deficient mutant (Quaking affected) mice and the Dittermate controls. We plan to examine the effect of changes in body temperature on BAEP latencies in Quaking affected mice and littermate controls.